Abstract 15183: Genetic Obesity and the Risk of Atrial Fibrillation - Causal Estimates From Mendelian Randomization
Introduction: Observational studies have identified an association between body mass index (BMI) and incident atrial fibrillation (AF). Inferring causality from observational studies, however, is subject to residual confounding and bias.
Objective: To utilize BMI-associated genetic variation to evaluate the causality of the association between BMI and AF.
Methods: Mendelian randomization with instrumental variable analysis was used to estimate cohort-specific causal hazard ratios for the association between BMI and AF in a total of 51,646 individuals from seven prospective population-based cohorts from the United States, Iceland, and the Netherlands. 4,178 cases of incident AF were ascertained between 1987 and 2012. Exposures included BMI measured at study baseline and a genetic instrument (BMI gene score) comprised of 39 SNPs associated with BMI in GWAS. Cohort specific estimates were combined by random-effects, inverse variance weighted meta-analysis.
Results: In age and sex-adjusted analyses, BMI was significantly associated with incident AF [HR= 1.05 per kg/m2 (95% CI: 1.04-1.06); p<0.001]. A one unit increase in BMI gene score was equivalent to 1.05 kg/m2 in BMI (95% CI: 0.90-1.20; p<0.001), and the BMI gene score was significantly associated with incident AF [HR: 1.11 per 1-unit increase (95% CI: 1.05-1.18); p<0.001]. Adjustment for measured BMI attenuated the association between the BMI gene score and incident AF [HR 1.05 per 1-unit increase (95% CI: 0.99-1.12); p=0.06]. The meta-analyzed instrumental variable estimate for the causal association between BMI and incident AF was HR 1.11 per kg/m2 (95% CI: 1.05-1.17; p<0.001). (Figure). Multivariable adjustment did not substantially alter any of the findings.
Conclusions: These data support a causal link between increased BMI and incident AF. Public health initiatives targeting primordial prevention of obesity and weight reduction have the potential to significantly reduce AF incidence.
Author Disclosures: N.A. Chatterjee: None. F. Giulianini: None. B. Geelhoed: None. K.L. Lunetta: None. J.R. Misialek: None. M.N. Niemeijer: None. M. Rienstra: None. L. Rose: None. A.V. Smith: None. D.E. Arking: None. P.T. Ellinor: None. J. Heeringa: None. H. Lin: None. S.A. Lubitz: None. E.Z. Soliman: None. N. Verweij: None. A. Alonso: None. E.J. Benjamin: None. V. Gudnason: None. B.H. Stricker: None. P. Van Der Harst: None. D.I. Chasman: None. C.M. Albert: None.
- © 2016 by American Heart Association, Inc.